At present the treatment of patients who have suffered a recent ischemic stroke is unsatisfactory. There is evidence suggesting that biogenic amines are causally involved in the processes that ultimately result in tissue destruction. However, due to problems caused by animal models that are difficult to control and inadequate biochemical methods, many questions about the influences of biogenic amines in focal central nervous system ischemia have not been adequately answered. If it can be conclusively demonstrated that the biogenic amines serotonin and norepinephrine substantially influence central nervous system infarction, and since many drugs are capable of altering these neurotransmitters, it may be possible to devise pharmacological regimes that can arrest or minimize the damage. To perform these studies we propose to develop a rabbit spinal cord infarction model. We will then: 1) define the neuropathology of the lesion; 2) determine the effects of ischemia on spinal cord concentrations of biogenic amines, their related receptors, and energy metabolites (ATP, ADP, AMP, and phosphocreatine); 3) test whether pharmacological treatments can alter the neuropathological and biochemical course of events. At all stages we will correlate these findings with the clinical status of the animals. We believe that the rabbit spinal cord infarction model is uniquely well suited for study of focal ischemia of the central nervous system and that out manifold approach to the problem will result in the possibliity of developing a rational approach to stroke therapy.